Unlocking the mind's mysteries

Dr Murray Cairns believes tiny molecules in the brain may
be the key to understanding the causes of a perplexing neuropsychiatric
disorder.

The brain is the most complex of
organs, with 100 billion neurons each connected to up to 100,000 other neurons.
To understand how irregularity within that intricate network can lead to
schizophrenia, Dr Murray Cairns delves deep into the innermost workings of brain
cells, studying the effect that tiny molecules called microRNA have on the
function of genes.

"One of the main hypotheses around
schizophrenia is that during development of the brain there is a problem with the
ability of neurons to make connections with each other," Cairns explains. "My
focus is on the role of microRNA in brain development, looking in particular at
how they regulate gene expression – whether those genes are switched on or off
and what controls that activity. The central dogma of molecular biology is that
the gene makes RNA and RNA makes protein, but these microRNA can prevent that
protein being produced, effectively 'silencing' – or switching off – the gene."

MicroRNA molecules play a key role
in regulating genes but were not discovered by scientists until 1993 and have
only been intensively studied since the early 2000s. As a postdoctoral
scientist, Cairns was part of a commercial biotechnology research team at the
forefront of that movement. "It was a high-powered group of researchers with cutting-edge
skills in gene delivery and gene suppression technology, so it was a great
training ground," recalls Cairns, who completed a PhD in molecular
biologyat the University of New South
Walesin 1998.

A scientific and personal interest
in schizophrenia attracted him in 2005to
a Schizophrenia Research Institute (SRI) fellowship at the University of
Newcastle. Cairns now leads his own research team, which last
year achieved a breakthrough by identifying a number of microRNA on chromosome
14 that are depleted in the blood of schizophrenia sufferers. The discovery has
the potential to lead to the development of a blood biomarker for
schizophrenia, which could assist in earlier diagnosis of the disorder, as well
as better predictions of susceptibility and likely response to treatments. The
finding of this genetic signature was published in the journal Molecular Psychiatry. Cairns and his team
are now extending their research into the causes of this down-regulation and
its impact on gene expression.

As well as ongoing support from the SRI and the Hunter Medical Research
Institute (HMRI), Cairns has received substantial grants from the US-based National Alliance for Research on Schizophrenia and Depression (NARSAD) and the National Health and
Medical Research Council (NHMRC), which awarded him $485,000 in 2010 to lead research
into the molecular and cellular characterisation of
schizophrenia-associated dysfunction in microRNA. Another $573,660 NHMRC grant received this year, administered through
the Brain and Mind Research Institute, will allow Cairns and his collaborators
to progress to a biological evaluation of microRNA involved in schizophrenia.

While scientists
remain confounded by the causes of schizophrenia, a mental illness that affects
one per cent of people worldwide, Cairns believes research is drawing closer to
unlocking the mysteries of the disorder.

"We know
schizophrenia has a large genetic component but researchers have been unable to
pin it on any one gene," he states. "Also, it is a disease that doesn't have
any obvious neuropathology – it doesn't produce lesions on the brain like
Parkinson's or Alzheimer's disease – so it is much harder to examine
scientifically.

"What does seem
obvious is that it is the result of a network dysfunction – a problem in the
brain's wiring – and that is what my research is investigating, right down to
the very molecular level."